Two pathways of specific cell mediated (complement independent) cytotoxicity occur in vitro: 1) antibody dependent cytotoxicity which occurs when antibody against target cells is added to a mixture of normal lymphoid cells and target cells, and 2) antibody independent cytotoxicity caused by sensitized T cells which injure target cells in the absence of antibody. The first pathway is mediated only by specific IgG; however, prior incubation of effector cells with normal IgG (i.e. IgG antibody not directed against target cell antigen) inhibits this pathway of cytotoxicity but not the pathway caused by sensitized T cells. By taking advantage of this differential effect of normal IgG, it is demonstrated that cells from an immunized individual can cause cytotoxicity by the first as well as the second pathway. Based on these preliminary findings, our objectives are to: 1) assess the role that free haptens, antireceptor (anti-idiotypic) antibody and specific non IgG antibodies may have in blocking or interfering with antibody dependent cell mediated cytotoxicity in vitro, and 2) assess the role that antibody dependent cell mediated cytotoxicity may play in vivo in the complex responses to grafts, tumors or in some "autoimmune" diseases.